Actinobacillus actinomycetemcomitans is a Gram-negative oral pathogen that is the etiologic agent of localized aggressive periodontitis. This bacterium can also cause several systemic diseases including infective endocarditis. As one of virulence factors, A. actinomycetemcomitans produces leukotoxin that kills human leukocytes and can also destroy erythrocytes. Our recent work strongly suggests that leukotoxin interacts with Cu, Zn superoxide dismutase (Cu, Zn SOD) from A. actinomycetemcomitans. Bacterial Cu, Zn SODs have a role in protecting pathogens from the oxidative damage caused by host inflamatory cells. Cu, Zn SOD has also been shown to bind heme and potentially play a role in iron and heme acquisition by bacteria. The proposed studies seek to understand the role of Cu, Zn SOD in A. actinomycetemcomitans. 1. I will study the interaction between Cu, Zn SOD and leukotoxin from A. actinomycetemcomitans. 2. I will characterize Cu, Zn SOD function in A. actinomycetemcomitans. This study will expand our knowledge of the physiology and pathogenesis of A. actinomycetemcomitans and may lead to a better understanding of the interplay between different putative virulence factors of an important oral pathogen.